EU GMP附录15确认和验证.docx

1、EU GMP附录15确认和验证EUROPEAN COMMISSIONENTERPRISEDIRECTORATE-GENERALSingle market, regulatory environment, industries under vertical legislationPharmaceuticals and cosmeticsBrussels,30 March 2015EudraLexVolume 4EU Guidelines forGood Manufacturing Practice forMedicinal Products for Human and Veterinary Us

2、eAnnex 15: Qualification and ValidationEU GMP附录15：确认和验证Legal basis for publishing the detailed guidelines:Article 47 of Directive 2001/83/EC on the Community code relating to medicinal products for human use and Article 51 of Directive 2001/82/EC on the Community code relating to veterinary medicina

3、l products. This document provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/EC for medicinal products for human use and Directive 91/412/EEC for veterinary use.公布详细指南的法律依据：指令2001/83/

4、EC第47款关于人药共同体代码，和2001/82/EC第51款关于兽药共同体代码的要求。本文件为指令2003/94/EC中制订的人药GMP以及指令91/412/EEC兽药GMP原则和指南提供诠释。Status of the document: Revision文件状态：修订Reasons for changes:Since Annex 15 was published in 2001 the manufacturing and regulatory environment has changed significantly and an update is required to this A

5、nnex to reflect this changed environment. This revision to Annex 15 takes into account changes to other sections of the EudraLex, Volume 4, Part I, relationship to Part II, Annex 11, ICH Q8, Q9, Q10 and Q11, QWP guidance on process validation, and changes in manufacturing technology.变更理由：自从附录15在2001

6、年公布以来，生产和法规环境已发生了重大变化，有必要对此附录进行更新以反映环境的变化。本次对附录15的修订考虑了欧洲药事法卷4第一部分其它部分的变化，与第二部分、附录11、ICH Q8 Q9 Q10以及Q11、QWP的工艺验证指南的关系，以及生产技术的变化。Deadline for coming into operation:1 October 2015最后实施时间：2015年10月1日Principle原则This Annex describes the principles of qualification and validation which are applicable to the

7、 facilities, equipment, utilities and processes used for the manufacture of medicinal products and may also be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, Part II. It is a GMP requirement that manufacturers cont

8、rol the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. Any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, should be formally documented and the i

9、mpact on the validated status or control strategy assessed. Computerised systems used for the manufacture of medicinal products should also be validated according to the requirements of Annex 11. The relevant concepts and guidance presented in ICH Q8, Q9, Q10 and Q11 should also be taken into accoun

10、t.本附录描述了确认和验证的原则，该原则适用于药品生产用设施、设备、公用系统和工艺，也可用作活性物质的可选补充指南，但并不对欧盟药事法第4卷第二部分引入附加要求。GMP要求生产商通过在产品和工艺的整个生命周期中进行确认和验证，对其操作关键方面进行控制。所有可能影响产品质量的设施、设备、公用系统和工艺计划变更均应进行正式记录，并评估其对验证状态和控制策略的影响。用于药品生产的计算机化系统也应根据附录11的要求进行验证。同时还应考虑ICH Q8 Q9 Q10和Q11是的相关概念和指南要求。General通则A quality risk management approach should be a

11、pplied throughout the lifecycle of a medicinal product. As part of a quality risk management system, decisions on the scope and extent of qualification and validation should be based on a justified and documented risk assessment of the facilities, equipment, utilities and processes. Retrospective va

12、lidation is no longer considered an acceptable approach. Data supporting qualification and/or validation studies which were obtained from sources outside of the manufacturers own programmes may be used provided that this approach has been justified and that there is adequate assurance that controls

13、were in place throughout the acquisition of such data.质量风险管理的方法应贯穿药品的整个生命周期。作为质量风险管理系统的一部分，决定确认和验证的范围和程度时应基于对设施、设备、公用系统和工艺的论证和书面风险评估。回顾性验证不再被认为是可以接受的方法。如果经过论证，并且获得数据的整个过程有足够控制保证，也可以使用从生产商自身程序以外获得的用于支持确认和/或验证研究的数据。1.ORGANISING AND PLANNING FOR QUALIFICATION AND VALIDATION1.确认和验证的组织和计划1.1.All qualific

14、ation and validation activities should be planned and take the life cycle of facilities, equipment, utilities, process and product into consideration.1.1.所有确认和验证活动应进行计划，并考虑设施、设备、公用系统、工艺和产品的生命周期1.2.Qualification and validation activities should only be performed by suitably trained personnel who foll

15、ow approved procedures.1.2.确认和验证活动应由经过适当培训的人员实施，并遵守已批准的程序1.3.Qualification/validation personnel should report as defined in the pharmaceutical quality system although this may not necessarily be to a quality management or a quality assurance function. However, there should be appropriate quality ove

16、rsight over the whole validation life cycle.1.3.确认/验证实施人员应根据药品质量体系中指定的要求进行报告，尽管并不一定是报告给质量管理或质量保证部门。但是，对整个验证生命周期应有适当的质量监管。1.4.The key elements of the site qualification and validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent document.1.4.应在验证主

17、计划（VMP）或等同的文件中界定和记录工厂确认和验证程序的关键要素1.5.The VMP or equivalent document should define the qualification/validation system and include or reference information on at least the following:1.5.VMP或对等的文件中应定义确认/验证体系，并包括或引用至少以下信息：i.Qualification and Validation policy;i.确认和验证方针ii.The organisational structure in

18、cluding roles and responsibilities for qualification and validation activities;ii.组织结构，包括确认和验证活动中的工作和职责iii.Summary of the facilities, equipment, systems, processes on site and the qualification and validation status;iii.现场设施、设备、系统、工艺总结和确认和验证状态iv.Change control and deviation management for qualificat

19、ion and validation;iv.确认和验证变更控制和偏差管理v.Guidance on developing acceptance criteria;v.可接受标准建立指南vi.References to existing documents;vi.对已有文件的引用vii.The qualification and validation strategy, including requalification, where applicable.vii.确认和验证策略，适当时应包括再确认1.6.For large and complex projects, planning take

20、s on added importance and separate validation plans may enhance clarity1.7.对于大型的复杂项目，增加计划重点和独立的验证计划将有助于明晰要做的工作1.8.A quality risk management approach should be used for qualification and validation activities. In light of increased knowledge and understanding from any changes during the project phase

21、 or during commercial production, the risk assessments should be repeated, as required. The way in which risk assessments are used to support qualification and validation activities should be clearly documented.1.9.在确认和验证活动中应使用质量风险管理方法。鉴于项目期间或商业生产期间所有变更导致对工艺的理解和知识的增加，在需要时应重复风险评估。应清楚记录用于支持确认和验证活动的风险评

22、估方法。1.10.Appropriate checks should be incorporated into qualification and validation work to ensure the integrity of all data obtained.1.11.应将适当的检查结合进确认和验证工作，以保证所获得的数据的完整性2.DOCUMENTATION, INCLUDING VMP文件记录，包括VMP2.1. Good documentation practices are important to support knowledge management throughou

23、t the product lifecycle.优良文件规范在支持整个产品周期中的知识管理方面是很重要的。2.2. All documents generated during qualification and validation should be approved and authorised by appropriate personnel as defined in the pharmaceutical quality system.所有在确认和验证期间产生的文件应由药品质量体系中指定的适当的人员批准和授权。2.3. The inter-relationship between d

24、ocuments in complex validation projects should be clearly defined.复杂验证项目中文件之间的内在关系应清楚界定。2.4. Validation protocols should be prepared which defines the critical systems, attributes and parameters and the associated acceptance criteria.应制订验证方案，在其中界定关键系统、属性和参数以及相关的可接受标准。2.5. Qualification documents may

25、 be combined together, where appropriate, e.g. installation qualification (IQ) and operational qualification (OQ).确认文件在适当时可以合并在一起，例如，安装确认（IQ）和运行确认（OQ）。2.6. Where validation protocols and other documentation are supplied by a third party providing validation services, appropriate personnel at the man

26、ufacturing site should confirm suitability and compliance with internal procedures before approval. Vendor protocols may be supplemented by additional documentation/test protocols before use.如果验证方案和其它文件记录由验证服务第三方提供，则应由生产场所的适当人员对文件记录的适用性进行确认，在批准前确认其符合内部程序。供应商方案在使用前可以进行文件记录/测试增补。2.7. Any significant c

27、hanges to the approved protocol during execution, e.g. acceptance criteria, operating parameters etc., should be documented as a deviation and be scientifically justified.在实施期间，对已批准的方案进行任何重大变更，例如，可接受标准、操作参数等，均应记录为偏差并经过科学论证。2.8. Results which fail to meet the pre-defined acceptance criteria should be

28、 recorded as a deviation and be fully investigated according to local procedures. Any implications for the validation should be discussed in the report不符合既定可接受标准的结果应记录为偏差，并根据内部程序进行全面调查。验证产生的影响应在报告里讨论。2.9. The review and conclusions of the validation should be reported and the results obtained summar

29、ised against the acceptance criteria. Any subsequent changes to acceptance criteria should be scientifically justified and a final recommendation made as to the outcome of the validation.对验证进行的审核及所得出的结论应报告，所得到的结果应进行总结并与可接受标准对照。所有之后对可接受标准的变更应经过科学论证，对验证的结果应做出最后的建议。2.10. A formal release for the next s

30、tage in the qualification and validation process should be authorised by the relevant responsible personnel either as part of the validation report approval or as a separate summary document. Conditional approval to proceed to the next qualification stage can be given where certain acceptance criter

31、ia or deviations have not been fully addressed and there is a documented assessment that there is no significant impact on the next activity.在确认和验证过程中，应由相关责任人授权对一个阶段结果进行放行，指示可以进入一下阶段。该放行可以是验证报告批准的一部分，也可以是一份单独的总结文件。如果对某些可接受标准或偏差还没能进行全面说明，但进行了书面评估说明对下一阶段活动没有重大影响，则可以有条件的批准进入下一验证阶段。3. QUALIFICATION STAGES FOR EQUIPMENT, FACILITIES, UTILITIES AND SYSTEMS.设备、设施、公用系统和系统的确认阶段3.1. Qualification activities should